Establishment of rat model of liver cirrhosis or liver cancer and its magnetic resonance images before and after superparamagnetic iron oxide enhancement
目的建立大鼠肝硬化肝癌模型,研究肝硬化背景下超顺磁性氧化铁纳米粒(SPIO)增强前后肝癌的检出率,并分析SPIO在大鼠肝硬化肝癌诱发过程中不同病变组织内分布变化情况,探讨其用于评估肝脏Kupffer细胞功能的可行性。方法 30只雄性SD大鼠按完全随机分组的方法分成实验组20只和对照组10只,实验组予0.1 mg/ml的二乙基亚硝胺(DENA)溶液自由饮用,对照组饮用灭菌生理盐水。实验组分别于给药后第10、20周各取10只先进行磁共振(MR)平扫,再注入SPIO后1 h行MR增强扫描,大鼠扫描完成后立即处死。同理,对照组10只于第20周MR扫描完成后立即处死。分析MR图像,取血标本进行肝功能测定,取肝脏标本进行HE和普鲁士蓝染色病理学检查。两组间均数比较采用成组t检验,多组间均数比较采用方差分析,率的比较采用卡方检验。相关性分析采用Pearson’s相关分析。结果较之对照组,大鼠的AST及ALT 10周组明显升高,20周组显著升高,3者间差异有统计学意义(P均<0.001)。注入SPIO 1 h后增强扫描,肝脏组织信号强度下降百分比(PSIL)最大为正常肝组织,单纯性肝硬化、远癌肝...Abstract:
Objective To establish a rat model of liver cirrhosis or liver cancer, to determine the liver cancer detection rates of magnetic resonance imaging ( MRI) in liver cirrhosis before and after superparamagnetic iron oxide ( SPIO) enhancement, to analyse the changes in SPIO distribution in different lesions in the process of inducing liver cirrhosis and liver cancer in rats, and to investigate the feasibility of assessing the function of Kupffer cells by SPIO- enhanced MRI. Methods Thirty male Sprague- Dawley ( SD) rats were randomly divided into experimental group ( n = 20) and control group ( n = 10) . The experimental group was given 0. 1 mg / ml diethylnitrosamine ( DENA) solution by free drinking, while the control group drank sterilized saline. At 10 or 20 weeks after treatment, 10 rats were selected from the experimental group to undergo plain MRI scans and then SPIO- enhanced MRI performed one hour after injection of SPIO; the rats were sacrificed immediately after scans. At 20 weeks after treatment, the 10 rats in control group underwent MRI scans and were then sacrificed immediately. The obtained MR images were analyzed. Blood samples were taken to measure serum alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) levels. Liver samples were taken and subjected to HE staining and Perls' blue staining for pathological examination. Results Compared with the control group, the experimental group had significantly increased ALT and AST levels at 10 weeks ( P <0. 001) , and the ALT and AST levels were significantly higher at 20 weeks than at 10 weeks in the experimental group ( P < 0. 001) . The SPIO- enhanced MRI showed that the percentage of signal intensity loss ( PSIL) was the highest in normal liver tissue, followed by simple cirrhosis tissue and cirrhosis tissue distant from liver cancer, and was the lowest in liver cancer tissue; there were significant differences in PSIL between the four tissues ( P < 0. 001) . In the experimental rats examined at 20 weeks after treatment, the liver cancer detection rate on each sequence and lesion- to- liver contrast- to- noise ratio increased significantly after SPIO enhancement ( P < 0. 05) . The Perls' blue staining showed that there was a significant linear correlation between the number of blue dye particles and PSIL on each sequence after SPIO enhancement in various liver tissues ( P < 0. 01) . Conclusion DENA induces the SD rat model of liver cirrhosis or liver cancer by the process similar to the development and progression of liver cirrhosis and liver cancer in humans. SPIO- enhanced MRI not only can indirectly reflect the changes in number and function of Kupffer cells in various lesions, but is also conducive to the early detection of liver cancer nodules in liver cirrhosis, with important value and guiding significance for clinical treatment.
- liver cirrhosis /
- liver neoplasms /
- magnetic resonance imaging /
EFFENDI K, SAKAMOTO M.Molecular patjology in early hepatocarcinogenesis[J].Oncology, 2010, 78 (2) :157-160. JIE SW, YANG LM, CHEN J, et al.Chitosan-poly (acrylic acid) magnetic microspheres prepared by in situ polymerization method and their characterization[J].J Chem Eng Chin Univ, 2008, 22 (5) :850-854. (in Chinese) 揭少卫, 杨黎明, 陈捷, 等.原位聚合法制备壳聚糖/聚丙烯酸水凝胶磁微球及其性能表征[J].高校化学工程学报, 2008, 22 (5) :850-854. QIAN Y, LING CQ.Preventive effect of Ganfujian granule on experimental hepatocarcinoma in rats[J].World J Gastroenterol, 2004, 10 (5) :755-757. JIAO ZY, LI C, MA ZL, et al.A primary study on the phagocytic activity of Kupffer cells with superparamagnetic iron oxide particles enhanced MR imaging in a rat nonalcoholic steatohepatitis model[J].Chin J Radiol, 2010, 44 (4) :430-433. (in Chinese) 焦志云, 李澄, 马占龙, 等.超顺磁性氧化铁MR成像评估大鼠非酒精性脂肪肝炎枯否细胞功能的初步研究[J].中华放射学杂志, 2010, 44 (4) :430-433. YI T, YAMASHITA Y, ARAKAWA A, et al.Detection of hepatocellular carcinoma arising in cirrhotic livers:comparison of gadoliniumandyerumoxides-enhanced MR imaging[J].AJR Am J Roentgend, 1999, 172 (6) :1547-1554. SUN Y, ZHENG YY, WU W, et al.Influence of superparamagnetic iron oxide loaded polymermicrospheres on enhanced MRI for liver cancer of rabbits[J].Chin J Med Imaging Technol, 2012, 28 (8) :1445-1448. (in Chinese) 孙阳, 郑元义, 吴伟, 等.载超顺磁性氧化铁高分子微球对兔肝癌MR成像效果的影响[J].中国医学影像技术, 2012, 28 (8) :1445-1448. NAITO M, HASEGAWA G, EBE Y, et al.Differentiation and function of Kupffer cells[J].Med Electron Microsc, 2004, 37 (1) :16-18. WANG MY, LI XH, HE TS, et al.Study on the role of Kupffer cells in the carcinogenesis of experimental liver carcinoma of kunming mouse[J].J Clin Res, 2012, 29 (7) :1261-1263. (in Chinese) 王梦远, 李旭宏, 何天时, 等.枯否细胞在昆明小鼠实验性肝癌发生中的作用及机制[J].医学临床研究, 2012, 29 (7) :1261-1263. CANBAY A, FELDSTEIN AE, HIGNCHI H, et al.Kupffer cell engnlfment of apoptotic bodies stimulates death ligand and cytokine expression[J].Hepatology, 2003, 38 (5) :1188-1198. TANIMOTO A, YUASA Y, SHINMOTO H, et al.Superparamagnetic iron oxide-mediated hepatic signal intensity change in patient with and without cirrhosis:pulse sequence effects and kupffer cell function[J].Radiology, 2002, 222 (3) :661-666. CHEN G, LUO DZ, GUO F, et al.Significance of CD68 (+) cells in primary hepatocellular carcinoma, paraneoplastic and cirrhosis tissues[J].Chin J Diagn Pathol, 2005, 12 (2) :141-142. (in Chinese) 陈罡, 罗殿中, 郭芳, 等.原发性肝细胞癌、癌旁及肝硬化组织中CD68 (+) 细胞的研究[J].诊断病理学杂志, 2005, 12 (2) :141-142. TERASAKI S, KANEKO S, KOBAYASHI K, et al.Histological features predicting malignant transformation of nonmalignant hepatocellular nodules:A prospective study[J].Gastroenterology, 1998, 115 (5) :1216-1222. ELIZONDO G, WEISSLCDER R, STARK D, et al.Hepatic cirrhosis and hepatitis:MR imaging enhanced with Superparamagnetic iron oxide[J].Radiology, 1990, 174 (5) :797-801. YANG LJ, QI NX, ZHAO CL.Study on correlation between expression of CD68 and MRI during the course of induced hepatocellular carcinoma by diethylnitrosamine in SD rats[J].J Pract Radiol, 2008, 24 (12) :1698-1701. (in Chinese) 杨立娟, 齐乃新, 赵彩蕾.二乙基亚硝胺诱发SD大鼠原发性肝细胞癌形成过程中CD68的表达与MRI表现的相关性实验研究[J].实用放射学杂志, 2008, 24 (12) :1698-1701.
- 文章访问数: 2970
- HTML全文浏览量: 4
- PDF下载量: 593
- 被引次数: 0